Serine/threonine kinases are members of the eukaryotic protein kinase superfamily. Enzymes of this class specifically phosphorylate serine or threonine residues of intracellular proteins and are important in mediating signal transduction in multicellular organisms. Many serine/threonine kinases occur as intracellular proteins which take part in signal transduction within the cell, including signal transduction to the nucleus and the activation of other proteins.
As such, phosphorylation of serine or threonine by serine/threonine kinases is an important mechanism for regulating intracellular events in response to environmental changes. A wide variety of cellular events are regulated by serine/threonine kinases. A few examples include the ability of cells to enter and/or complete mitosis, cellular proliferation, cellular differentiation, the control of fat metabolism, immune responses, inflammatory responses and the control of glycogen metabolism.
An important superfamily of cell membrane receptors is the group known as G-protein coupled receptors (GPCR), known also as seven trans-membrane receptors (7TM). This superfamily of receptors is involved in the transmission of signals that originate from low molecular weight ligands such as adrenaline or from peptide ligands such as chemokines and a variety of hormones such as melanocyte stimulating hormone (MSH).
Numerous studies have shown that intracellular protein kinases which specifically interact with various members of the 7TM receptors are able to desensitize them and thereby decrease or eliminate the signal transmission effected 7TM. These protein kinases are known as G-protein-coupled receptor kinases (GRKs), which are serine/threonine kinases. So far, six of these kinases have been discovered (GRK1–6). Some of the GRKs are restricted to a small number of tissues (e.g., GRK1), while GRK2 and GRK 3, known also as β-ARK1 and β-ARK2 are ubiquitously expressed. A comprehensive review is provided, for example, by M. Bunemann and M. M. Hosey, “G-Protein Coupled Receptor Kinases as Modulators of G-Protein Signalling,” J ofPhysiology, Vol. 517(1):5–23 (1999).
Syndrome X is a term coined in 1988 by Stanford University Endocrinologist Dr. Gerald Risson, that describes a group of symptoms including: high blood pressure, abdominal obesity, insulin resistance, high levels of triglycerides and low levels of HDL, low levels of anti-oxidant vitamins and DHEA, high cortisone levels, as well as depression. Some experts estimate that as many as two-thirds of Americans may be suffering from syndrome X, although it may be effectively hidden for years masquerading as symptoms for other conditions such as fatigue, poor mental concentration, abdominal obesity, edema, nerve damage and intense craving for sweets.